The present invention relates generally to systems for high speed analysis of combinatorial libraries by contacting a plurality of library members simultaneously with a test fluid under high pressures, and more particularly, to an apparatus and method for screening library members based on each member's ability to catalyze the conversion of fluid reactants.
Combinatorial chemistry refers to methods for creating chemical libraries—vast collections of compounds of varying properties—that are tested or screened in order to identify a subset of promising compounds. Depending on how they are made, libraries may consist of substances free in solution, bound to solid supports, or arrayed on a solid surface.
The advent of combinatorial chemistry promises to change the discovery and development of new and useful materials. For example, workers in the pharmaceutical industry have successfully used such techniques to dramatically increase the speed of drug discovery. Material scientists have employed combinatorial methods to develop novel high temperature superconductors, magnetoresistive materials, and phosphors. More recently, scientists have applied combinatorial methods to catalyst development. See, for example, U.S. Pat. No. 5,985,356 “The Combinatorial Synthesis of Novel Materials” and U.S. Pat. No. 6,030,917 “Combinatorial Synthesis and Analysis of Organometallic Compounds and Catalysts”, which are both herein incorporated by reference in their entirety.
Once a researcher creates a combinatorial library, he or she must screen tens, hundreds or even thousands of compounds. Existing analytical methods and devices, which were originally designed to characterize a relatively small number of compounds, are often ill-suited to screen combinatorial libraries. This is true in catalyst research where, up until now, there has been little need to rapidly test or characterize large numbers of compounds at one time.
In traditional catalyst development, for example, researchers synthesize relatively large amounts of a candidate compound. They then test the compound to determine whether it warrants further study. For solid phase catalysts, this initial testing involves confining the compound in a pressure vessel, and then contacting the compound with one or more fluid phase reactants at a particular temperature, pressure and flow rate. If the compound produces some minimal level of reactant conversion to a desired product, the compound undergoes more thorough characterization in a later step.
Because synthesis consumes a large fraction of the development cycle in traditional catalyst studies, researchers have expended little effort to speed up the screening step. Thus, although test reactors have been steadily improved over the years, most were simply automated to reduce labor needed to operate them. Even automated catalyst screening devices comprised of multiple reaction vessels were operated sequentially, so that the reaction time for a group of candidate compounds was about the same as could be achieved with a single-vessel reactor.
Conventional catalyst screening devices have other problems as well. For example, traditional experimental fixed bed reactors require relatively large catalyst samples. This makes them impracticable for screening combinatorial libraries. With combinatorial methods, one obtains increased chemical diversity at the expense of sample size. Individual library members may therefore consist of no more than a milligram (mg) or so of material. In contrast, conventional fixed bed reactors typically require 10 g or more of each candidate compound.
Recently, parallel fixed bed reactors have been developed to address many of these problems. See, for example, U.S. Pat. No. 6,149,882 “Parallel Fixed Bed Reactor And Fluid Contacting Apparatus and Method”, and co-pending U.S. patent application Ser. No. 11/145,050 (Publication No. 2006-0006065) “Microfluidic Fluid Distribution Manifold For Use With Multi-Channel Reactor Systems” both of which are herein incorporated by reference in their entirety. However the pressure and temperature operating parameters of these reactor systems are limited by the various components such as seals, valves, etc.
High pressure sealing at elevated temperatures (typically above about 1000 psig and 100° C.) of fluid valves (especially gas) is difficult due to the high pressure differential of the sealed fluid to atmosphere. High contact loads are typically required at seal surfaces which limit the ability of the valve to have the moving parts required for directing the gases to various ports.
The present invention overcomes, or at least minimizes, one or more of the problems set forth above.